Quantification of mesembrine and mesembrenone in mouse plasma using UHPLC-QToF-MS: Application to a pharmacokinetic study.

Quantification of mesembrine and mesembrenone in mouse plasma using UHPLC-QToF-MS: Application to a pharmacokinetic study.
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使用 UHPLC-QToF-MS 定量小鼠血浆中的 mesembrine 和 mesembrenone:在药代动力学研究中的应用。

DOI:
10.1002/bmc.3815
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发表时间:
2017
期刊:
Biomedical chromatography : BMC
影响因子:
--
通讯作者:
Khan,ShabanaI
Khan,ShabanaI
中科院分区:
--
文献类型:
--
作者:
Manda,VamshiK;Avula,Bharathi;Ashfaq,MohammadK;Abe,Naohito;Khan,IkhlasA;Khan,ShabanaI

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鬼针草是一种南非本土草本植物,被广泛用作治疗焦虑和压力的草药补充剂。在提取物中存在两种主要的药理活性生物碱,即中膜酮和中膜碱。尽管红花提取物具有广泛的治疗应用,但目前还没有关于这两种重要生物碱在血浆中的药代动力学性质或分析方法的报道。因此,本研究旨在建立和验证一种简便、灵敏的同时测定小鼠血浆中的系膜酮和系膜的分析方法。采用超高效液相色谱-质谱仪(UHPLC/QToF-MS)来实现我们的目标。以奎宁为内标,甲醇(100%)蛋白沉淀法提取。两种化合物的定量下限均为10 ng/m L。两种化合物的萃取回收率均在87%~93%之间,对分析无基质影响。所有质控样品的准确度在89.5%~106%之间,精密度为12.6%。该方法被成功地应用于静脉注射的评价。小鼠中膜和中膜酮的血浆药代动力学。然而,这些生物碱的口服生物利用度较差,血药浓度低于检测限值。
Sceletium tortuosum, is an indigenous herb of South Africa which is widely used as an herbal supplement in the treatment of anxiety and stress. Mesembrenone and mesembrine are the two main pharmacologically active alkaloids present in the extract. Despite the wide therapeutic applications ofSceletiumextract, there are no reports ofin vivopharmacokinetic properties or analytical methods to quantify these two important alkaloids in plasma. Therefore, the current study aimed to develop and validate a simple and sensitive analytical method for simultaneous quantification of mesembrenone and mesembrine in mouse plasma. Ultra‐high‐performance liquid chromatography–mass spectrometry (UHPLC/QToF‐MS) was employed to achieve our objectives. The compounds were extracted using protein precipitation by methanol (100%) with quinine as an internal standard. The lower limit of quantification for both the compounds was 10 ng/mL. The extraction recovery was between 87 and 93% for both compounds with no matrix effects on the analysis. The accuracy was between 89.5 and 106% and precision was <12.6% for all quality control samples. This validated method was successfully applied to evaluate the i.v. plasma pharmacokinetics of mesembrine and mesembrenone in mouse. However, the oral bioavailability of these alkaloids was poor and the plasma levels were below the detection limits.